Functions of a PEBP2 transcription factor in T lymphocyte specific gene expression.

Pebpb2基因编码异二聚体转录因子PEBP2/CBF的一个非dna结合亚基，并在与人类急性髓性白血病相关的16号染色体倒置中重排。为了研究Pebpb2的生理功能，我们采用靶向策略对其进行突变，产生一个零突变体。小鼠的纯合突变在E12.5左右的胚胎中被证明是致命的，显然是由于中枢神经系统的大量出血。此外，肝脏的决定性造血功能严重受损。观察到的表型与报道的AML1纯合破坏无法区分，AML1编码PEBP2/CBF的DNA结合亚基。因此，研究结果表明，这两个亚基在体内作为异二聚体PEBP2/CBF共同发挥作用，PEBP2/CBF在最终造血的发展中起着至关重要的作用。

The Pebpb2 gene encodes a non-DNA binding subunit of the heterodimeric transcription factor, PEBP2/CBF and is rearranged in inversion of chromosome 16 associated with human acute myeloid leukemia. To investigate its physiological function, Pebpb2 was mutated by a targeting strategy to generate a null mutant. The homozygous mutation in mice proved lethal in embryos around E12.5, apparently due to massive hemorrhaging in the central nervous system. In addition, definitive hematopoiesis in the liver was severely impaired. The observed phenotype was indistinguishable from that reported for homozygous disruption of AML1, which encodes a DNA binding subunit of PEBP2/CBF.Thus, the results indicate that the two subunits function together as a heterodimeric PEBP2/CBF in vivo and that PEBP2/CBF plays an essential role in development of definitive hematopoiesis.